背景:在祖先血统引起的第一次COVID-19波后,新的SARS-CoV-2变种的不断涌现助长了大流行。了解每个新出现的关注变体的关键事件发生时间周期至关重要,因为它可以提供对病毒未来轨迹的见解,并有助于为疫情准备和响应计划提供信息。这里,我们的目标是研究潜伏期,串行间隔,和世代时间已从祖先的SARS-CoV-2谱系变为不同的变体。
方法:我们进行了系统综述和荟萃分析,综合了潜伏期的估计值,串行间隔,和祖先谱系的生成时间(包括实现的和内在的),阿尔法,Beta,和SARS-CoV-2的Omicron变体。
结果:我们的研究包括从147个家庭研究中获得的280条记录,接触追踪研究,或已知流行病学联系的研究。随着每个新兴的变体,我们发现每个分析的关键事件时间周期都在逐渐缩短,尽管我们没有发现Omicron亚变体之间的统计学差异。我们发现OmicronBA.1对潜伏期的汇总估计值最短(3.49天,95%CI:3.13-4.86天),串行间隔的OmicronBA.5(2.37天,95%CI:1.71-3.04天),和OmicronBA.1用于实现的生成时间(2.99天,95%CI:2.48-3.49天)。对于Omicron亚变体,只有一个内在生成时间的估计:对于OmicronBA.1.,只有6.84天(95%CrI:5.72-8.60天)。对于每个调查的关键事件发生时间,祖先谱系的汇总估计值最高。与病毒谱系的潜伏期相比,我们还观察到序列间隔的合并估计值较短。当汇集不同病毒谱系的估计时,我们发现了相当大的异质性(I2>80%;I2是指由于异质性而不是机会引起的研究中总变异的百分比),可能是由于不同研究群体之间的异质性(例如,部署干预措施,社会行为,人口特征)。
结论:我们的研究支持进行接触者追踪和流行病学调查以监测SARS-CoV-2传播模式变化的重要性。我们的发现强调了潜伏期的逐渐缩短,串行间隔,和生成时间,这可能导致流行病传播得更快,峰值发病率较大,更难控制。我们还一致发现序列间隔比潜伏期短,提示SARS-CoV-2的一个关键特征是症状前传播的可能性。这些观察结果有助于规划未来的COVID-19波。
After the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern.
We conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2.
Our study included 280 records obtained from 147 household studies, contact tracing studies, or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods, although we did not find statistically significant differences between the Omicron subvariants. We found that Omicron BA.1 had the shortest pooled estimates for the incubation period (3.49 days, 95% CI: 3.13-4.86 days), Omicron BA.5 for the serial interval (2.37 days, 95% CI: 1.71-3.04 days), and Omicron BA.1 for the realized generation time (2.99 days, 95% CI: 2.48-3.49 days). Only one estimate for the intrinsic generation time was available for Omicron subvariants: 6.84 days (95% CrI: 5.72-8.60 days) for Omicron BA.1. The ancestral lineage had the highest pooled estimates for each investigated key time-to-event period. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. When pooling the estimates across different virus lineages, we found considerable heterogeneities (I2 > 80%; I2 refers to the percentage of total variation across studies that is due to heterogeneity rather than chance), possibly resulting from heterogeneities between the different study populations (e.g., deployed interventions, social behavior, demographic characteristics).
Our study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves.